Membrane-bound Dense-core Granules Research Articles

Two Different Types of Carcinoid Tumors of the Lung: Immunohistochemical and Ultrastructural Investigation and Their Histogenetic Consideration

Carcinoid tumors have been an interesting clinical and pathological entity for pathologists because of their unique histopathologic pattern of “Zellballen” (cell ball) and the hormones they produce demonstrable by histochemical and biochemical methods, including immunohistochemistry, and the presence of cytoplasmic dense-core particles demonstrable by electron microscopy. Since carcinoid tumors were established as an entity more than a century ago by Oberndorfer, who was credited with coining the term “carcinoid,” meaning carcinoma-like tumors, tumors presenting with similar characteristics have been reported in most of parenchymal organs, including lungs.Carcinoid tumors in the lungs usually occur as bronchocentric tumors and present with typical histopathologic characteristics of carcinoid tumors, but they may present with significant variation in their cellular compositions, in contrast to the midgut carcinoid tumors. In the latter, tumor cells are quite similar to enterochromaffin granule containing c...

Nasal Neuroendocrine Carcinoma in a Free-Living Japanese Raccoon Dog ( Nyctereutes procyonoides viverrinus)

Neuroendocrine carcinoma was diagnosed in the left nasal cavity of a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus). Microscopically, the tumour consisted of sheets of anaplastic cells separated by narrow zones of fibrovascular stroma. The neoplastic cells had varying numbers of cytoplasmic granules stained by the Grimelius method. Immunohistochemically, the neoplastic cells were variably labelled for cytokeratin AE1/AE3, vimentin, chromogranin A and S-100. Ultrastructurally, some of the neoplastic cells had cytoplasmic membrane-bound dense-core granules of approximate diameter 140-240nm. The tumour had infiltrated the cerebrum and metastasized to the pituitary gland, mandibular and pulmonary lymph nodes, lungs, thyroid gland and adrenal glands.

Askin tumor with metastasis to the scalp: a histochemical, immunohistochemical and ultrastructural study

A 29-year-old woman presented with facial edema, and imaging disclosed a tumor extending from the anterior chest wall to the anterosuperior aspect of the mediastinum. Transbronchial cytology of the primary tumor and biopsy of the metastatic scalp lesion were performed. Histologically, the tumor consisted of closely packed small round cells. The neoplastic cells generally had round nuclei, finely dispersed chromatin, and small to prominent nucleoli. Histochemically, the cytoplasm of the neoplastic cells contained abundant glycogen and stained with Grimelius silver. Immunohistochemically, the neoplastic cell membranes reacted with CD99 (MIC2) and the neoplastic nuclei reacted with Fli-1, but various other markers, including lymphocyte and skeletal muscle markers, were not detected. No neoplastic cells were also reactive for chromogranin A, synaptophysin, and neurofilament. Ultrastructurally, some neoplastic cells had delicate cytoplasmic processes and contained membrane-bound dense core granules in the cytoplasm. Even if results are immunohistochemically negative for neuroendocrine markers, the combination of immunohistochemistry of CD99 (MIC2) and Fil-1 may be useful in diagnosing Askin tumor or its metastatic lesion.

Neuroendocrine (carcinoid) tumor of the mandible: A case report and review of the literature

The aim of this article is to present a case of primary neuroendocrine tumor (typical carcinoid) of the mandible that occurred in a 46-year-old black woman who was seropositive for the human immunodeficiency virus. Radiologically the lesion presented as a poorly circumscribed honeycomb radiolucency that extended from tooth 21 to the ascending ramus. Histologically the tumor cells were variously arranged in small islands, trabeculae, follicles, and slitlike spaces lined by a single layer of palisaded low-columnar cells. The follicles contained an eosinophilic colloid-like substance. Immunocytochemical staining showed diffuse, intense positivity for MAK 6, pancytokeratin, S-100, and neuron-specific enolase and focal, intense, positive staining for chromogranin A. Electron microscopy showed the presence of interdigitating cell membranes, rudimentary cell attachments, and varying numbers of membrane-bound dense core granules. Special investigations failed to reveal a primary tumor, and no metastases were found. Urine and hematologic assessment did not show any evidence of functional activity. The tumor was resected, and no recurrence or spread has been seen for 2 years. Origin from foregut-derived, immature, and functionally uncommitted endocrine cells is presumed.

Colloid cysts of the third ventricle: ultrastructural features are compatible with endodermal derivation.

The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron-lucent cytoplasm and scattered membrane-bound dense-core granules (150-350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium.

New observations of colloid cysts of the third ventricle: An ultrastructural study of the lining epithelium and the wall

Colloid cysts of the third ventricle represent one of the variety of the epithelial-lined cysts of the neuraxis. Their histogenesis remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroectoderm, including paraphysis, ependyma, choroid plexus, and tela choroidea and (b) endoderm, including respiratory and enteric epithelium.This report describes the ultrastructure of the lining epithelium and the wall of four cases of colloid cyst. Six distinct cell types were recognized in the epithelium (Fig.1,2): (1) ciliated cells with various types of ciliary abnormalities, (2) non-ciliated cells with microvilli coated with granulo-fibrillary material, (3) goblet cells showing discharge of secretory granules, (4) basal cells with prominent tonofilaments, (5) basal-located cells with elongated cell bodies parallel to the basement membrane and electron-lucent cytoplasm containing sparse, membrane-bound dense core granules (150-250 nm) and (6) small undifferentiated cells with scanty organelles.

COLLOID CYSTS OF THE THIRD VENTRICLE

The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron-lucent cytoplasm and scattered membrane-bound dense-core granules (150–350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium.

Merkel Cell Carcinoma: A Challenge

A 70-year-old man presented with an enlarging, recurrent tumor of the left buttock which, on initial biopsies, was interpreted as a histiocytic malignant lymphoma. Further biopsies showed numerous monomorphic, hyperchromatic, noncohesive cells, arranged in compact sheets, throughout the dermis, the fat, and the underlying muscle. Neuron specific enolase stain for neuroendocrine granules was positive. Electron microscopy showed cytoplasmic perinuclear microfilaments and round membrane-bound dense core granules. The histologic, enzymatic, and ultrastructural findings confirmed the diagnosis of Merkel cell carcinoma. Early diagnosis and treatment are imperative for a favorable outcome.

Criteria for the diagnosis of primary endocrine carcinoma of the skin (merkel cell carcinoma). A histological, immunohistochemical and ultrastructural study of 13 cases

Thirteen cases of primary endocrine carcinoma of the skin (Merkel cell carcinoma) were reviewed with the aim of defining the morphological, immunohistochemical and ultrastructural criteria for diagnosis. The tumour cells were characterized by their scanty cytoplasm, generally small uniform nuclei with finely dispersed chromatin and multiple small nucleoli. Nuclear shapes varied from round to spindle, with larger and pleomorphic forms predominating in 2 tumours. A striking feature seen in 12 tumours was the occurrence of a "ball-in-mitt" pattern represented by 1 or 2 crescentic tumour cells closely wrapped around an oval cell. Staining for neuron-specific enolase was the most consistent marker of the tumour and the characteristic juxtanuclear globular staining for keratin and cytokeratin and the occasional coexpression of neurofilament set this tumour apart from other cutaneous neoplasms, in particular, metastatic carcinoid tumours and oat cell carcinoma from the lung. The fine structural features of note were striking paranuclear or juxtanuclear whorls of intermediate filaments, seen in 7 cases, the presence of variable numbers of membrane-bound dense core granules of 80-150 nm diameter in all cases and cytoplasmic spinous or microvillous projections containing microfilaments in 4 cases. Less consistent characteristics of primary endocrine carcinomas of the skin included cell moulding, argyrophilia and immunohistochemical staining for ACTH, VIP and calcitonin. The high frequency of vessel invasion in this series is in keeping with the high rate of local recurrence, lymph node metastases and visceral dissemination reported. The distinction from other similar appearing tumours in the skin is discussed.

Ultrastructure of Merkel corpuscles and so-called "transitional" cells in the white Leghorn chicken.

In the chicken Merkel corpuscles are located in the dermis and consist of specialized Merkel cells, discoid nerve endings and lamellar cells. Merkel cells contain characteristic membrane-bound dense-core granules and bundles of microfilaments. Asymmetric junctions, synapse like, with thickened membranes and clusters of dense-core vesicles were observed between the Merkel cells and the nerve endings. The nerve ending is derived from myelinated nerves and sometimes contains clusters of clear vesicles. A laminar system formed by lamellar cells of the Schwann cell type encloses the Merkel cells and the nerve endings. So called "transitional" cells, showing some of the morphological features of both keratinocytes and Merkel cells, were observed in the basal layer of the epidermis. One was located partly in the epidermis and partly in the dermis. The structure of Merkel corpuscles is compared with that of Merkel cells in other tetrapods. The developmental significance of "transitional" cells and the origin of Merkel cells are discussed.

The Fusion of Merkel Cell Granules with a Synapse-Like Structure

The fusion of the membrane-bound dense-core granules of the Merkel cell with a synapse-like structure between the Merkel cell and its associated nerve fiber was observed. This fusion might imply that the tactile sensation by the Merkel cell is mediated by the release of the content of the membrane-bound dense-core granules into the specialized synapse-like structure.